The role of regional conduction delay and myocardial heterogeneity in the origin of clinical arrhythmias and sudden death is suspected but difficult to prove. We intend to investigate the electrical properties of myocardium in three canine models of acute and chronic injury: local K ion perfusion, regional ischemia (transmural and subendocardial), and chronic alcoholism. The K ion perfusion model reproduces the electrical changes usually associated with acute regional ischemia, including ST segment elevation and cardiac arrhythmias, while the chronically alcoholic dog offers a type of gradually developed more diffuse injury for investigation. Each of these models has been extensively utilized in our laboratory. We will define the electrical changes in conduction velocity, excitability and automaticity of tissues inside, at the border of and outside of the injured region (in the K ion and ischemic models) and correlate them with local electrolyte alterations and regional blood flow. Since transmural gradients of electrolytes and flow are present during ischemia, and at least the electrolyte gradient is demonstrable in the K ion perfused region, differential alterations in inner and outer walls will be sought. To reproduce the clinical circumstances often associated with the onset of arrhythmias in man, the electrical and metabolic effects of acute changes in heart rate, blood pressure and sympathetic stimulation will be investigated in these models. Finally, as we have been able to prevent or delay ventricular tachycardia and fibrillation with appropriate use of antiarrhythmic drugs in the K ion perfused myocardium, we intend to extend our investigations to determine the local changes responsible for these modifications.